The drug rofecoxib (Vioxx), an anti-inflammatory drug used for arthritis, was previously taken off the US market because of serious cardiovascular side effects.
However, new research has found that the class of drugs known as COX-2 inhibitors may yet be made safer.
COX-2 inhibitors are used to reduce arthritis pain. Another arthritis treatment in the same class, called diclofenac, became restricted last month by the UK’s prescription drug regulator over similar side effect concerns – although it is still recommended for use in people with arthritis pain, as long as they do not also have serious underlying heart conditions.
A new international research study that could help make this group of drugs safer was carried out by researchers at Imperial College London and published today.
The study looked into how these arthritis treatments work and found that their effect on an enzyme known as COX-2 – hence their name – happens in certain parts of the body, if the effect in mice is indicative of the effect in humans.
The researchers say their work “has revealed that COX-2 is largely absent from the major blood vessels and instead found in the brain, gut and kidney, as well as the thymus gland in the chest.”
Knowing this, the researchers predict, will facilitate the development of more targeted arthritis drugs that do not carry the more serious side effects, making their benefits against pain worthwhile.
The cardiovascular risks, such as heart attack and stroke in some people, was previously attributed to COX-2 being found in the blood vessels, the researchers explain. But this new study suggests this is not true, finding that the effect may actually be in the brain, gut, kidney and thymus gland.
Professor Jane Mitchell of Imperial College London’s Faculty of Medicine is lead author of the research findings and says they may shed more light on how serious side effects could be removed for future drugs:
“Now we know the true sites of COX-2, we can begin to develop new ideas that will lead to better drugs for arthritis and cancer.”
Professor Mitchell added: “This study does not provide all the answers, but once we understand exactly how COX-2 affects the cardiovascular system, we will be in a position to design new therapies. This will not be easy but all the tools are available and we could be looking at new leads within 5 to 10 years.”
To accurately measure concentrations of COX-2 within the body, the researchers used mice whose COX-2 gene had been replaced with a gene called luciferase, which gives fireflies their distinctive glow.
The lab work allowed researchers to create detailed images of the distribution of COX-2 throughout the body.
Professor Mitchell’s co-author Professor Anna Nicolaou, now at the University of Manchester, said: “This study is the first to use such sophisticated techniques to determine the locations of COX-2 within the body. The use of mass spectrometry and genetically modified mice in this way represents a significant advance in the field.”
Another co-author, Professor Tim Warner from the University of London, added weight to the researchers’ claims of groundbreaking methods:
“These cutting edge techniques are at last supplying us with the definitive answers we need to understand the side effects of arthritis drugs. This could help improve therapy for many millions of patients worldwide.”
The research was funded by the Wellcome Trust, a global charitable foundation established in Britain to improve human and animal health.